was diagnosed with a rare neuromuscular disorder

called amyotrophic lateral sclerosis, or ALS.

Gradually, he lost the ability to walk,

use his hands,

move his face,

and even swallow.

But throughout it all, he retained his incredible intellect,

and in the more than 50 years that followed,

Hawking became one of history's most accomplished and famous physicists.

However, his condition went uncured

and he passed away in 2018 at the age of 76.

Decades after his diagnosis,

ALS still ranks as one of the most complex,

mysterious,

and devastating diseases to affect humankind.

Also called motor neuron disease and Lou Gehrig's Disease,

ALS affects about two out of every 100,000 people worldwide.

When a person has ALS,

their motor neurons,

the cells responsible for all voluntary muscle control in the body,

lose function and die.

No one knows exactly why or how these cells die

and that's part of what makes ALS so hard to treat.

In about 90% of cases,

the disease arises suddenly, with no apparent cause.

The remaining 10% of cases are hereditary,

where a mother or father with ALS passes on a mutated gene to their child.

The symptoms typically first appear after age 40.

But in some rare cases, like Hawking's, ALS starts earlier in life.

Hawking's case was also a medical marvel because of how long he lived with ALS.

After diagnosis, most people with the disease live between 2 to 5 years

before ALS leads to respiratory problems that usually cause death.

What wasn't unusual in Hawking's case was that his ability to learn,

think,

and perceive with his senses remained intact.

Most people with ALS do not experience impaired cognition.

With so much at stake for the 120,000 people

who are diagnosed with ALS annually,

curing the disease has become one of our most important scientific

and medical challenges.

Despite the many unknowns,

we do have some insight into how ALS impacts the neuromuscular system.

ALS affects two types of nerve cells called the upper and lower motor neurons.

In a healthy body, the upper motor neurons,

which sit in the brain's cortex,

transmit messages from the brain to the lower motor neurons,

situated in the spinal cord.

Those neurons then transmit the message into muscle fibers,

which contract or relax in response,

resulting in motion.

Every voluntary move we make occurs

because of messages transmitted along this pathway.

But when motor neurons degenerate in ALS,

their ability to transfer messages is disrupted,

and that vital signaling system is thrown into chaos.

Without their regular cues, the muscles waste away.

Precisely what makes the motor neurons degenerate

is the prevailing mystery of ALS.

In hereditary cases, parents pass genetic mutations on to their children.

Even then, ALS involves multiple genes

with multiple possible impacts on motor neurons,

making the precise triggers hard to pinpoint.

When ALS arises sporadically, the list of possible causes grows:

toxins,

viruses,

lifestyle,

or other environmental factors may all play roles.

And because there are so many elements involved,

there's currently no single test that can determine whether someone has ALS.

Nevertheless, our hypotheses on the causes are developing.

One prevailing idea is that certain proteins inside the motor neurons

aren't folding correctly,

and are instead forming clumps.

The misfolded proteins and clumps may spread from cell to cell.

This could be clogging up normal cellular processes,

like energy and protein production, which keep cells alive.

We've also learned that along with motor neurons and muscle fibers,

ALS could involve other cell types.

ALS patients typically have inflammation in their brains and spinal cords.

Defective immune cells may also play a role in killing motor neurons.

And ALS seems to change the behavior of specific cells

that provide support for neurons.

These factors highlight the disease's complexity,

but they may also give us a fuller understanding of how it works,

opening up new avenues for treatment.

And while that may be gradual, we're making progress all the time.

We're currently developing new drugs,

new stem cell therapies to repair damaged cells,

and new gene therapies to slow the advancement of the disease.

With our growing arsenal of knowledge,

we look forward to discoveries that can change the future

for people living with ALS.